Distribution of calcitonin gene-related peptide in the rat peripheral nervous system with reference to its coexistence with substance P

Lee, Y.; Takami, Kenji; Kawai, Yoshinori; Girgis, S. I.; Hillyard, C. J.; MacIntyre, I.; Emson, Piers C.; Tohyama, Masaya

doi:10.1016/0306-4522(85)90265-9

Cited by 422 publications

(128 citation statements)

References 12 publications

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“…As expected, both CGRP and substance P immunoreactivities were generally localized in smaller neurons and were present infrequently in large, neurofilament-IR neurons. These data on the proportion of adult DRG neurons with these neuropeptides were similar to those in other reports (Lee et al, 1985;Tuchscherer and Seybold, 1985;Kai-Kai et al, 1986;Boehmer et al, 1989;Noguchi et al, 1990).…”

Section: Cgrp-ir Neurons and The Intensity Of Neuropeptide Immunoreacsupporting

confidence: 91%

“…Neuropeptides are often found in small DRG neurons that can innervate skin and viscera, whereas abundant neurofilament expression is characteristic of large neurons that innervate muscle spindles (Lawson et al, 1984;Perry et al, 1991). The neuropeptides CGRP and substance P are usually found in small neurons but can be contained in sensory neurons of varied sizes (Gibson et al, 1984;Lee et al, 1985;Skofitsch and Jacobowitz, 1985;Gibbins et al, 1987;Marti et al, 1987;Molander et al, 1987;Lawson, 1989, 1990;O'Brien et al, 1989). The coexistence of particular peptides in specific subpopulations of DRG neurons is related to peripheral targets.…”

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confidence: 99%

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The Generation of Neuronal Heterogeneity in a Rat Sensory Ganglion

Hall

Hickman

et al. 1997

J. Neurosci.

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Adult sensory neurons differ chemically, morphologically, and functionally, but the factors that generate their diversity remain unclear. For example, neuropeptides are generally found in small neurons, whereas abundant neurofilament is common in large neurons. Neurons containing the neuropeptides calcitonin gene-related peptide (CGRP) or substance P were quantified using immunohistochemistry in rat lumbar dorsal root ganglion (DRG) at times before and after sensory neurons contact central and peripheral targets in vivo. No neurons in the newly formed DRG expressed neuropeptide or neuropeptide mRNA, but neuropeptides were detectable about the time that axons connect with peripheral targets. To determine the requirement for target in neuropeptide regulation, embryonic DRG neurons were isolated at times before central and peripheral connections had formed, placed in culture, and immunocytochemically assayed for CGRP and substance P. Cultured neurons expressed neuropeptides with a time course and in proportions similar to those in vivo. Thus, some neurons in the embryonic DRG seem to be intrinsically specified to later express CGRP and substance P. The percentage of CGRP-immunoreactive neurons was not changed by cell density, non-neuronal cells, neurotrophins in addition to nerve growth factor (NGF), or antibody inactivation of neurotrophin-3 in the presence of NGF. To test the role of extrinsic cues on CGRP expression, DRG neurons were co-cultured with potential target tissues. Coculture with a rat epidermal or smooth muscle cell line increased the proportion of CGRP-containing neurons, whereas primary skeletal muscle and 3T3 cells had no effects. Thus, multiple appropriate sensory neuron phenotypes arise in a regulated fashion in cultured neurons isolated before target connections have formed, and some candidate target tissues can modulate that intrinsic expression pattern. Key words: neuropeptides; substance P; calcitonin generelated peptide; neurofilament; nociceptive; sensory ganglion; target tissue; skin; neurotrophinA striking feature of the adult vertebrate sensory nervous system is the diversity of neuronal cell types that perform together to maintain homeostasis and convey information about the environment. During development, specific neurons must be generated in appropriate locations and connect discretely to both peripheral targets and the CNS for functional integrity. Thus, it is important to understand not only how the phenotype is generated but also how neurons match targets. This study examines the developmental regulation of sensory neurons containing calcitonin generelated peptide (CGRP) that predominantly contact visceral and cutaneous peripheral target end organs in vivo.Adult rat sensory neurons can express neuromodulatory neuropeptides, but the factors that regulate their initial expression remain unknown. Cutaneous afferents appear in rat proximal hindlimb on embryonic days 14 -15 (E14 -E15) and in skin of distal toes at E16 -E17 (Reynolds et al

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Section: Cgrp-ir Neurons and The Intensity Of Neuropeptide Immunoreacsupporting

confidence: 91%

mentioning

confidence: 99%

The Generation of Neuronal Heterogeneity in a Rat Sensory Ganglion

Hall

Hickman

et al. 1997

J. Neurosci.

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“…In mammals, the major location of CGRP and its specific receptor is in the central and peripheral nervous system. (41)(42)(43) The wide distribution of CGRP in the brain suggests a function as neuromediator or neuromodulator and involvement in various brain functions. (44)(45)(46) CGRP appears to play a similar role as neuromediator or neuromodulator in sauropsids and amphibians.…”

Section: Discussionmentioning

confidence: 99%

Involvement of calcitonin and its receptor in the control of calcium-regulating genes and calcium homeostasis in zebrafish (Danio rerio)

Lafont

Wang

Chen

et al. 2010

Journal of Bone and Mineral Research

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Calcitonin (CT) is one of the hormones involved in vertebrate calcium regulation. It has been proposed to act as a hypocalcemic factor, but the regulatory pathways remain to be clarified. We investigated the CT/calcitonin gene-related peptide (CGRP) family in zebrafish and its potential involvement in calcium homeostasis. We identified the presence of four receptors: CTR, CRLR1, CRLR2, and CRLR3. From the phylogenetic analysis, together with the effect observed after CT and CGRP overexpression, we concluded that CTR appears to be a CT receptor and CRLR1 a CGRP receptor. The distribution of these two receptors shows a major presence in the central nervous system and in tissues involved in ionoregulation. Zebrafish embryos kept in high-Ca 2þ -concentration medium showed upregulation of CT and CTR expression and downregulation of the epithelial calcium channel (ECaC). Embryos injected with CT morpholino (CALC MO) incubated in high-Ca 2þ medium, showed downregulation of CTR together with upregulation on ECaC mRNA expression. In contrast, overexpression of CT cRNA induced the downregulation of ECaC mRNA synthesis, concomitant with the downregulation in the calcium content after 30 hours postfertilization. At 4 days postfertilization, CT cRNA injection induced upregulation of hypercalcemic factors, with subsequent increase in the calcium content. These results suggest that CT acts as a hypocalcemic factor in calcium regulation, probably through inhibition of ECaC synthesis. ß

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“…Substance P and CGRP are present in C-fibres and coexist in up to 20% of dorsal root ganglion (DRG) neurones (Lee et al, 1985). Expression of both peptides is modulated by NGF in adult sensory neurone cultures (Lindsay & Harmar, 1989;, and both are upregulated during inflammation (Noguchi et al, 1988;Donaldson et al, 1992;Donnerer et al, 1992;Smith et al, 1992;Woolf et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Contribution of interleukin‐1β to the inflammation‐induced increase in nerve growth factor levels and inflammatory hyperalgesia

Safieh‐Garabedian

Poole

Allchorne

et al. 1995

British J Pharmacology

556

324

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Peripheral inflammation is associated with the local production of neuroactive inflammatory cytokines and growth factors. These may contribute to inflammatory pain and hyperalgesia by directly or indirectly altering the function or chemical phenotype of responsive primary sensory neurones. To investigate this, inflammation was produced by the intraplantar injection of complete Freund's adjuvant (CFA) in adult rats. This resulted in a significant elevation in interleukin‐ip (IL‐1β) and nerve growth factor (NGF) levels in the inflamed tissue and of the peptides, substance P and calcitonin gene‐related peptide (CGRP) in the L4 dorsal root ganglion 48 h post CFA injection. The effects of a steroidal (dexamethasone) and a non‐steroidal (indomethacin) anti‐inflammatory drug on the levels of NGF and IL‐1β in inflamed tissue were investigated and compared with alterations in behavioural hyperalgesia and neuropeptide expression in sensory neurones. Systemic dexamethasone (120 μg kg−1 per day starting the day before the CFA injection) had no effect on the inflammatory hyperalgesia. When the dose was administered 3 times daily, a reduction in mechanical and to a lesser extent thermal sensitivity occurred. Indomethacin at 2 mg kg−1 daily (i.p.) had no effect on the hyperalgesia and a dose of 4 mg kg−1 daily was required to reduce significantly mechanical and thermal hypersensitivity. The increase in NGF produced by the CFA inflammation was prevented by both dexamethasone and indomethacin, but only at the higher dose levels. Dexamethasone at the lower and higher dose regimes diminished the upregulation of IL‐1β whereas indomethacin had an effect only at the higher dose. The increase in SP and CGRP levels produced by the CFA inflammation was prevented by dexamethasone and indomethacin at the lower and higher dose regimes. Intraplantar injections of IL‐1β (0.01, 0.1 and 1 ng) produced a brief (6 h) thermal hyperalgesia and an elevation in cutaneous NGF levels which was prevented by pretreatment with human recombinant IL‐1 receptor antagonist (IL‐1 ra) (0.625 μg, i.v.). The thermal hyperalgesia but not the NGF elevation produced by intraplantar IL‐1β (1 ng) was prevented by administration of a polyclonal neutralizing anti‐NGF serum. IL‐1 ra significantly reduced the mechanical hyperalgesia produced by CFA for 6 h after administration as well as the CFA‐induced elevation in NGF levels. Anti‐NGF pretreatment substantially reduced CFA‐induced mechanical and thermal hyperalgesia without reducing the elevation in IL‐1β. Intraplantar NGF (0.O2, 0.2 and 2 μg) injections produced a short lasting thermal and mechanical hyperalgesia but did not change IL‐1β levels in the hindpaw skin. Our results demonstrate that IL‐1β contributes to the upregulation of NGF during inflammation and that NGF has a major role in the production of inflammatory pain hypersensitivity.

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Distribution of calcitonin gene-related peptide in the rat peripheral nervous system with reference to its coexistence with substance P

Cited by 422 publications

References 12 publications

The Generation of Neuronal Heterogeneity in a Rat Sensory Ganglion

The Generation of Neuronal Heterogeneity in a Rat Sensory Ganglion

Involvement of calcitonin and its receptor in the control of calcium-regulating genes and calcium homeostasis in zebrafish (Danio rerio)

Contribution of interleukin‐1β to the inflammation‐induced increase in nerve growth factor levels and inflammatory hyperalgesia

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